Retraction: Fahr Disease: A Rare Cause of First-Time Seizure in the Emergency Department.

[This retracts the article DOI: 10.7759/cureus.19965.].

Detecting and Mapping N6-Methyladenosine on RNA/DNA Hybrids.

N6-methyladenosine (m6A) is an RNA modification essential for posttranscriptional regulation of gene expression in eukaryotes. We recently demonstrated that m6A decorates the RNA components of R-loops, specific nucleic acid structures consisting of an RNA/DNA hybrid and a single strand of non-template DNA, that represent a major source of genetic instability and, at the same time, contribute to regulation of gene expression in mammalian cells. According to growing body of experimental evidence, adenosine methylation affects stability of these structures and potentially influences various aspects of their metabolism. Here, we present two methods for detection and analysis of m6A-containing RNA/DNA hybrids: an immunostaining protocol allowing investigation of their spatial distribution in eukaryotic cells and m6A-DNA immunoprecipitation (DIP), an antibody-based technique that permits their genome mapping and locus-specific analysis. In addition to the m6A-focused studies, these methodologies can also contribute to elucidating the functional roles of other RNA modifications in R-loop biology.

Analysis of 5-Carboxylcytosine Distribution Using DNA Immunoprecipitation.

DNA methylation (5-methylcytosine, 5mC) is involved in regulation of a wide range of biological processes. TET proteins can oxidize 5mC to 5-hydroxymethylcytosine, 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). Although both 5fC and 5caC serve as intermediates in active demethylation pathway, growing body of experimental evidence indicate that these DNA modifications may also interact with specific sets of reader proteins and therefore may represent bona fide epigenetic marks. Despite a number of single-base resolution techniques have recently been proposed for 5fC/5caC mapping, antibody-based approaches still represent a relatively simple and plausible alternative for the analysis of genomic distribution of these DNA modifications. Here, we describe a protocol for 5caC DNA immunoprecipitation (5caC DIP) that can be used for both locus-specific and genome-wide assessment of 5caC distribution. In combination with mass spectrometry-based techniques and single base resolution mapping methods, this approach may contribute to elucidating the role of 5caC in development, differentiation, and tumorigenesis.

Fahr Disease: A Rare Cause of First-Time Seizure in the Emergency Department.

Seizure is a common neurological problem in the emergency department. First-time seizure needs careful evaluation to exclude the underlying structural brain lesions. Neuroimaging studies, including magnetic resonance imaging and computed tomography scan, are strongly recommended for all adult patients with first-time seizures. We report the case of a 35-year-old woman who was brought to the emergency department because of the first-time loss of consciousness episode. She developed bilateral jerky movements in both her upper and lower limbs. It was associated with frothy secretions from the mouth and cyanosis. The episode lasted for two minutes and terminated spontaneously. The patient was tired after gaining consciousness. The past medical history of the patient was remarkable for anxiety, depression, and polycystic ovarian syndrome. She has undergone multiple cognitive behavioral therapy sessions, but she did not take any psychiatric medications. Neurological examination did not reveal any focal neurological deficit. The patient underwent a computed tomography scan to exclude any space-occupying lesion. The unenhanced scan demonstrated bilateral symmetrical calcification of the basal ganglia. No calcification was noted in the cerebellum or the cerebral cortex. Otherwise, no intracranial pathology was seen. Such findings conferred the diagnosis of Fahr disease. The patient was discharged on carbamazepine to prevent further seizure episodes. After six months of follow-up, the patient did not experience further convulsion episodes. Fahr disease is a rare disorder with a wide spectrum of manifestations. Despite its rarity, physicians should keep this condition as a possible differential diagnosis when they encounter an adult patient with a first-time seizure, particularly in a patient with a history of neuropsychiatric disorders.

Efficacy and Safety of Pharmacoinvasive Strategy Compared to Primary Percutaneous Coronary Intervention in the Management of ST-Segment Elevation Myocardial Infarction: A Prospective Country-Wide Registry.

Background: A pharmacoinvasive reperfusion strategy is recommended for ST-elevation myocardial infarction (STEMI) patients when primary percutaneous coronary intervention (PCI) cannot be achieved in a timely fashion. This is based on a limited number of trials. The effectiveness of this strategy in the real-world is unclear. Objectives: To compare the effectiveness of pharmacoinvasive strategy versus primary PCI using a nationwide prospective registry of STEMI patients. Methods: We examined 936 STEMI patients from the reperfusion in ST-elevation myocardial infarction in Kuwait (REPERFUSE Kuwait) registry who underwent either primary PCI or pharmacoinvasive reperfusion. A composite outcome was measured based on death, congestive heart failure, reinfarction or stroke prospectively ascertained during hospital stay and up to one-year follow-up. The association between reperfusion strategy and the composite outcome was assessed using multivariate regression and Poisson proportional hazard model. Results: Compared to the pharmacoinvasive group, those undergoing primary PCI had higher Killip class on presentation and required more blood transfusions during hospitalization. There was no significant difference between primary PCI and pharmacoinvasive strategy with regards to the incidence of the composite outcome during the in-hospital period (RR = 1.0; 95% CI 0.98-1.02; p = 0.96) after adjustment for possible confounders. Over one-year follow-up, the survival of the two groups was not different (p = 0.66). The incidence of major bleeding was similar in both groups. Conclusion: STEMI patients treated with a pharmacoinvasive strategy have comparable outcomes to those treated with primary PCI with no increased risk of major bleeding. These real-world data support the use of a pharmacoinvasive strategy when primary PCI cannot be achieved in a timely fashion.

Disparity in ST-segment Elevation Myocardial Infarction Practices and Outcomes in Arabian Gulf Countries (Gulf COAST Registry).

OBJECTIVES: The objective of this study is to describe contemporary management and 1-year outcomes of patients hospitalized with ST-segment elevation myocardial infarction (STEMI) in Arabian Gulf countries. METHODS: Data of patients admitted to 29 hospitals in four Gulf countries [Bahrain, Kuwait, Oman, United Arab Emirates (UAE)] with the diagnosis of STEMI were analyzed from Gulf locals with acute coronary syndrome (ACS) events (Gulf COAST) registry. This was a longitudinal, observational registry of consecutive citizens, admitted with ACS from January 2012 to January 2013. Patient management and outcomes were analyzed and compared between the four countries. RESULTS: A total of 1039 STEMI patients were enrolled in Gulf COAST Registry. The mean age was 58 years, and there was a high prevalence of diabetes (47%). With respect to reperfusion, 10% were reperfused with primary percutaneous coronary intervention, 66% with fibrinolytic therapy and 24% were not reperfused. Only one-third of patients who received fibrinolytic therapy had a door-to-needle time of 30 min or less. The in-hospital mortality rate was 7.4%. However, we noted a significant regional variability in mortality rate (3.8%-11.9%). In adjusted analysis, patients from Oman were 4 times more likely to die in hospital as compared to patients from Kuwait. CONCLUSIONS: In the Gulf countries, fibrinolytic therapy is the main reperfusion strategy used in STEMI patients. Most patients do not receive this therapy according to timelines outlined in recent practice guidelines. There is a significant discrepancy in outcomes between the countries. Quality improvement initiatives are needed to achieve better adherence to management guidelines and close the gap in outcomes.

Design and Rationale of Gulf locals with Acute Coronary Syndrome Events (Gulf Coast) Registry.

OBJECTIVES: To describe the risk profile, management and one-year outcomes of patients hospitalized with acute coronary syndrome (ACS) in the Gulf region of the Middle East. SUBJECTS AND METHODS: The Gulf locals with acute coronary syndrome events (Gulf COAST) registry is a prospective, multinational, longitudinal, observational, cohort-based registry of consecutive citizens, from the Gulf region of the Middle East, admitted from January 2012 to January 2013 to 29 hospitals with a diagnosis of ACS. Data entered online included patient demographics, cardiovascular risk profiles, past medical history, physical findings on admission, in-hospital diagnostic tests and therapeutic management, as well as one year outcomes. RESULTS: 3188 patients were recruited. The mean age was 60.4 ± 12.6years (range: 22-112), 2104 (66%) were males and 1084 (34%) females. The discharge diagnosis was ST-segment elevation myocardial infarction (STEMI) in 741 (23.2%), new-onset left bundle branch block myocardial infarction (LBBBMI) in 30 (0.9%), non-ST-segment elevation myocardial infarction (NSTEMI) in 1486 (46.6%) and unstable angina in 931 (29.2%). At hospital presentation, 2105 (66%), 1779 (55.8%), 1703 (53.4%) and 740 (23.2%) had history of hypertension, dyslipidemia, diabetes mellitus and active smoking, respectively. CONCLUSION: Patients with ACS in our region are young with very high risk profile. The Gulf COAST registry is an example of successful regional collaboration and will provide information on contemporary management of ACS in the region.

Quality of anticoagulation with warfarin across Kuwait.

INTRODUCTION: Warfarin is widely used in patients with non-valvular atrial fibrillation (AF) because it is effective in reducing thromboembolic complications. However, it has a narrow safe therapeutic window. We aimed to examine the frequency of maintaining this therapeutic window in daily practice. METHODS: We enrolled consecutive patients with non-valvular AF presenting to five busy general hospitals in Kuwait for regular international normalised ratio (INR) testing. Patients were required to be on warfarin for more than 3 months and to have had at least 5 INR measurements. We recorded up to 20 INR measurements per patient. Time in therapeutic range (TTR) was assessed by the Rosendaal method and the percentage of INR measurements in the therapeutic range was recorded. RESULTS: A total of 369 patients with non-valvular AF underwent 4392 INR measurements. (mean age 62.89 ± 11 years, 56% women, 78% had hypertension and 58% had diabetes). Mean duration of warfarin use was 13 ± 9.1 months. Of all INR measurements, 47% were in the therapeutic range of 2-3 and TTR by Rosendaal method was 52.6%. CONCLUSIONS: The quality of anticoagulation with warfarin in non-selected daily practice in Kuwait is poor. This could have serious implications for patients' outcomes.

Adherence to ACC/AHA performance measures for myocardial infarction in six Middle-Eastern countries: association with in-hospital mortality and clinical characteristics.

BACKGROUND/OBJECTIVES: This study assesses adherence to performance measures for acute myocardial infarction (AMI) in six Middle-Eastern countries, and its association with in-hospital mortality. Few studies have previously assessed these performance measures in the Middle East. METHODS: This cohort study followed 5813 patients with suspected AMI upon admission to discharge. Proportions of eligible participants receiving the following performance measures were calculated: medications within 24 hours of admission (aspirin and beta-blocker) and on discharge (aspirin, beta-blockers, angiotensin converting enzyme inhibitors [ACEI], and lipid-lowering therapy), reperfusion therapy, and low-density lipoprotein (LDL) cholesterol measurement. A composite adherence score was calculated. Associations between performance measures and clinical characteristics were assessed using multivariate logistic regression. RESULTS: Adherence was above 90% for aspirin, reperfusion, and lipid-lowering therapies; between 60% and 82% for beta-blockers, ACEI, statin therapy, time-to-balloon within 90 minutes, and LDL-cholesterol measurement; and 33% for time-to-needle within 30 minutes. After adjustment, factors associated with high composite performance score (>85%) included Asian ethnicity (Odds Ratio, OR=1.3; p=0.01) and history of hyperlipidemia (OR=1.4; p=0.001). Factors associated with a lower score included atypical symptoms (OR=0.6; p=0.003) and high GRACE score (OR=0.6; p<0.001). Lower in-hospital mortality was associated with provision of reperfusion therapy (OR=0.54, p=0.047) and beta-blockers within 24 hours (OR=0.33, p=0.005). CONCLUSIONS: Overall adherence was lowest among the highest-risk patients. Lower in-hospital mortality was independently associated with adherence to early performance measures, comprising observational evidence for their effectiveness in a Middle East cohort. These data provide a focus for regional quality improvement initiatives and research.

Clinical characteristics and outcomes of patients with acute coronary syndrome and prior coronary artery bypass grafting in a large middle eastern cohort.

BACKGROUND: Acute Coronary Syndrome (ACS) can occur in patients with prior coronary artery bypass grafting (CABG). In the Gulf Registry of acute coronary events (Gulf RACE), we identified the clinical characteristics and in-hospital outcomes of these patients. METHODS: Clinical characteristics and in-hospital outcomes for 461 ACS patients with prior CABG are compared to 7715 ACS patients without prior CABG enrolled from 64 hospitals in 6 Gulf countries over a 6-month period. RESULTS: The overall incidence of ACS with prior CABG was 5.6% out of 8176 patients. The ACS with prior CABG were older (63 vs 55 years, P<0.0001), had more history of diabetes (62.3 vs 37.6%, P <0.0001), dyslipidemia (70.3 vs 29.5%, P<0.0001), and hypertension (75.7 vs 47.8%, P<0.0001) compared with the non-CABG group. They presented more frequently with dyspnea (14.8 vs 9.5%, P<0.0005), non-ST segment elevation myocardial infarction (41.4 vs 31.6%, P<0.0001) and echocardiographic evidence of left ventricular dysfunction (49.4 vs 29.8%, P<0.0001) than ACS without prior CABG. They had a complicated in-hospital course with more recurrent ischemia (13.9 vs 9.3%, P=0.0011), heart failure (24.1 vs 15.7%), and stroke (2.2 vs 0.6%) compared with those without CABG. The in-hospital mortality rate was 5.6% in the CABG group compared with 3.5% in the ACS without prior CABG group. After adjusting for confounders, prior CABG was independently associated with recurrent ischemia and shock, more in patients presenting with ST elevation than non-ST elevation ACS. CONCLUSIONS: Patients with ACS and prior CABG are a high-risk group with poor outcomes irrespective of their older age and comorbidities. They should be identified and treated differently to improve their outcomes.

Prevalence and impact of cardiovascular risk factors among patients presenting with acute coronary syndrome in the middle East.

The authors explored the prevalence and impact of the cardiovascular risk factors (CVRFs) in patients presenting with acute coronary syndrome (ACS). During a five-month period in 2007, six adjacent Middle Eastern countries participated in the Gulf Registry of acute coronary events. CVRFs were identified on admission. Patients' characteristics and in-hospital outcomes were analyzed across the types of ACS. Among 6704 consecutive patients with ACS, 61% had non-ST elevation ACS (NSTEACS) and 39% had ST-elevation myocardial infarction (STEMI). Female sex, old age, diabetes mellitus, hypertension, dyslipidemia, and obesity were more prevalent in NSTEACS patients. STEMI patients were more likely to be smokers and less likely to be taking aspirin prior to the index admission. Chronic renal failure (CRF) and diabetes mellitus were independent predictors of in-hospital heart failure in NSTEACS, while CRF and hypertension were predictors of STEMI. Female sex and CRF were independent predictors of mortality in STEMI (odds ratio, 2.0; 95% confidence interval, 1.19-3.13 and odds ratio, 5.0; 95% confidence interval, 3.47-7.73, respectively). Assessment of the prevalence of CVRF in the acute coronary presentation is of important prognostic value for in-hospital morbidity and mortality. CVRF and its impact may differ according to ACS type, age, and sex. Coronary heart disease (CHD) is the leading cause of mortality and morbidity worldwide. To achieve a significant reduction in the prevalence of CHD, it is essential to adopt effective preventive strategies with adequate awareness of the epidemiology of cardiovascular risk factors (CVRFs).1 CVRFs include traditional and nontraditional factors. However, the US Preventive Services Task Force concluded that the evidence is insufficient to assess the balance of benefits and harms of using nontraditional risk factors.2,3 The World Health Organization has recognized obesity, hypertension, hypercholesterolemia, and smoking among the top10 traditional risk factors for premature death and morbidity.4 Since these risk factors are usually evident before developing CHD, knowledge of their prevalence in a given population allows the prediction of the likely burden of CHD.3 The American Heart Association has recognized many risk factors; some can be modified, treated, or controlled and some can not.5 The more risk factors present, the greater the likelihood of developing CHD. Currently, most reports for prevention of CHD are mainly derived from European centers and suggest that risk factors for CHD are varying from country to country.6 However, data from the Arab Middle East that evaluate the prevalence and impact of these risk factors in acute coronary events are scarce.4,7,8 We explore the prevalence of CVRFs in patients with acute coronary syndrome (ACS) who are living in the Arab Middle East and the impact of these factors on in-hospital heart failure (HF) and mortality. Copyright © 2011 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.

Missed opportunities in the management of ST-segment elevation myocardial infarction in the Arab Middle East: patient and physician impediments.

BACKGROUND: Lack of timely reperfusion therapy in patients with ST-elevation myocardial infarction (STEMI) has been associated with worse outcomes. The aim of this study is to identify the frequency and predictors of delayed presentation and missed reperfusion in patients with STEMI in the Gulf Register of Acute Coronary Events (Gulf RACE) registry. Delayed Presentation and missed reperfusion is associated with increased in hospital mortality in STEMI patients. METHODS: Gulf RACE is a prospective, multinational study of all consecutive patients hospitalized with the final diagnosis of acute coronary syndrome in 65 centers in 6 Arab countries. In this analysis, we included 3197 patients with STEMI. The independent predictors of delayed presentation and missed reperfusion therapy were identified using multivariate logistic regression. RESULTS: In total, 929 patients presented > 12 hours after symptom onset. The independent predictors of late presentation are older age, atypical symptoms, no family history of coronary artery disease, and being in Yemen. Of the 2268 STEMI patients presenting early, a total of 205 patients (9.3%) did not receive reperfusion therapy despite no contraindications (shortfall). The independent predictors of not receiving appropriate reperfusion therapy are older age, prior stroke, being in Yemen, and atypical symptoms. Lack of reperfusion therapy due to shortfall or delayed presentation was associated with increased in-hospital mortality. CONCLUSIONS: Nearly one-third of patients with STEMI in the Arab Middle East present to the hospital > 12 hours after symptom onset, and nearly 1 in 10 eligible patients do not receive any reperfusion therapy. Community and physician awareness programs are needed to increase the utilization of appropriate lifesaving therapies.